Systems for gross processing of tissue samples and related methods

ABSTRACT

Tissue sample cassettes for receiving tissue samples include an upper tray including compartments separated by dividers, a lower tray coupled to the upper tray and having a central recess, and an absorbent material located in the recess of the lower tray. Related systems and methods for automated gross processing of tissue samples are also disclosed.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a divisional of U.S. patent application Ser. No.16/115,990, filed Aug. 29, 2018, titled “BIOPSY TISSUE SAMPLE CASSETTEAND RELATED SYSTEMS AND METHODS,” which claims the benefit of U.S.Provisional Patent Application No. 62/551,683, filed Aug. 29, 2017,titled “BIOPSY TISSUE SAMPLE CASSETTE AND RELATED SYSTEMS AND METHODS,”the entire disclosure of each of which is hereby incorporated by thisreference.

FIELD

Embodiments of the application relate to biopsy tissue sample cassettesfor gross processing of tissue samples within the tissue samplecassettes, including related systems and methods.

BACKGROUND

In biopsy processes, tissue samples are taken from a patient and placedin one or more compartments of a tissue sample cassette. The tissuesample cassette is often placed in a container containing formalin (anaqueous formaldehyde solution) or another liquid for chemical fixationand/or transportation to a pathology laboratory, where furtherprocessing (e.g., histology, grossing, fixation, dehydration,infiltration, embedding, microtome sectioning, staining, microscopicreview) of the tissue sample may take place. Alternatively, the tissuesamples may be transported in one or more formalin-filled bottles.

For some biopsy procedures, such as some needle-core biopsies, multipletissue samples are obtained from a patient's organ or other body areaand placed into respective tissue sample cassettes. When the pathologylaboratory receives the container including the tissue samples, thespecimen is typically logged into a manual or computerized anatomicpathology system and may be assigned a tracking number. This trackingnumber may be manually recorded or may be in the form of a bar code on alabel or sticker applied to biopsy containers and tissue preparationcassettes. As the specimen is logged into the system, a physicaldescription is provided by a pathologist or an assistant as part of thegross examination or “grossing” portion of processing the specimen.

SUMMARY

As will be described in greater detail below, the present disclosuredescribes devices, systems, and methods for tissue sample processing,such as for pathological procedures.

In one embodiment, the present disclosure includes tissue samplecassettes that include an upper tray with compartments separated bydividers in a top wall of the upper tray, a lower tray coupled to theupper tray, and an absorbent material located in a central recess of thelower tray. The central recess may be defined by sidewalls located on abase of the lower tray. The dividers of the upper tray may be locatedover an upper surface of the absorbent material. The compartments may besized and configured to retain tissue samples therein and over the uppersurface of the absorbent material.

In some examples, the tissue sample cassette may further include a coverreleasably secured to at least one of the upper tray or the lower tray.The cover may include indentations in an upper surface thereof. Theindentations may be sized and configured to respectively at leastpartially extend into the compartments of the upper tray. At least aportion of a lower surface of the cover proximate the upper tray mayinclude a hydrophobic material. At least a portion of the upper surfaceof the absorbent material may include a hydrophilic material. Each ofthe cover and the lower tray may include at least one tab to facilitateremoval of the cover from the lower tray. The dividers of the upper traymay include sidewalls including depth markers. Each of the compartmentsmay include an elongated opening in the top wall of the upper tray and arecess in a front wall configured to facilitate placement of the tissuesamples on the upper surface of the absorbent material through theelongated opening. The inner sidewalls of the dividers of the upper traymay include an upper vertical portion, a lower vertical portion, and aninclined portion between the upper vertical portion and the lowervertical portion. The upper tray may also include a front wall, a backwall opposite the front wall, a first sidewall, and a second sidewallopposite the first sidewall. The top wall of the upper tray may extendbetween the front wall, the back wall, the first sidewall, and thesecond sidewall. The top wall of the upper tray may also includealphanumeric indicators corresponding to the compartments. Each of thealphanumeric indicators may be located on the top wall of the upper traybetween the back wall of the upper tray and a distal end of a respectivecompartment.

In one example, the absorbent material may include an upper surface withat least one cutout sized and shaped for receiving a tissue sampletherein. The tissue sample cassette may also include a tracking element.The tracking element may be located on a lower surface of a base portionof the lower tray. The tracking element may be selected from the groupconsisting of a radio-frequency identification (RFID) tag, a barcodelabel, a written label, and a serial number label. The absorbentmaterial may include a pre-wetted sponge. A material forming the tissuesample cassette may be resistant to degradation when exposed to at leastone of formalin, an RNA preservative, saline solution, a chemicalfixative, and/or water. In one example, the compartments of the uppertray may each include an elongated compartment sized to receive aneedle-core biopsy tissue sample.

In some embodiments, the present disclosure includes systems forautomated gross processing of tissues samples in a tissue samplecassette. Such systems may include a multi-compartment tissue samplecassette including a tracking element, at least one imaging device, atracking element reader, and a processor. The at least one imagingdevice may be configured to obtain images of tissue samples positionedwithin respective compartments of the multi-compartment tissue samplecassette. The tracking element reader may be associated with the atleast one imaging device and may be configured to read information fromthe tracking element of the multi-compartment tissue sample cassette.The processor may be associated with the at least one imaging device andthe tracking element reader. The processor may be in communication withmemory configured to store the images of the tissue samples. Theprocessor may be programmed to recognize the tissue samples and todetermine and provide gross measurements for the tissue samples based onthe images of the tissue samples obtained with the at least one imagingdevice.

In some examples, the processor may be configured to accept informationassociated with the tracking element being read by the tracking elementreader. The processor may be configured to process informationassociated with records stored in a data storage unit. The grossmeasurements provided by the processor may include at least one ofheight, length, or area of the tissue samples.

In some embodiments, the present disclosure includes methods ofproviding gross measurements of tissue samples in a tissue samplecassette. In accordance with such methods, tissue samples may besupported with a multi-compartment tissue sample cassette. At least oneimage of the tissue samples may be acquired utilizing an imaging device.Gross measurements of the tissue samples may be determined using aprocessor programmed to recognize the tissue samples from the at leastone image and to provide the gross measurements based on the at leastone image.

In some examples, the acquired at least one image and the grossmeasurements may be linked with records using a tracking element readerconfigured to recognize a tracking element associated with themulti-compartment tissue sample cassette. The tissue samples may betransported with the tissue sample cassette to a pathology laboratorywithout the tissue samples being suspended in a fluid. In one example, aplurality of images of the tissue samples may be acquired with at leastone camera. In one example, the processor may be used to recognizetissue samples based on the acquired images and based at least in parton information stored in a data storage unit.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings illustrate a number of example embodiments andare a part of the specification. Together with the followingdescription, these drawings demonstrate and explain various principlesof the present disclosure.

FIGS. 1-8 illustrate various views of a tissue sample cassette accordingto an embodiment of the disclosure.

FIG. 1 shows a top perspective view of the tissue sample cassetteaccording to an embodiment of the disclosure.

FIG. 2 shows an exploded top perspective view of the tissue samplecassette of FIG. 1.

FIG. 3 shows a front view of the tissue sample cassette of FIG. 1.

FIG. 4 shows a back view of the tissue sample cassette of FIG. 1.

FIG. 5 shows a left side view of the tissue sample cassette of FIG. 1.

FIG. 6 shows a right side view of the tissue sample cassette of FIG. 1.

FIG. 7 shows a top plan view of the tissue sample cassette of FIG. 1.

FIG. 8 shows a bottom view of a tissue sample cassette of FIG. 1.

FIG. 9 is a simplified block diagram of an imaging system according toan embodiment of the disclosure.

DETAILED DESCRIPTION OF EXAMPLE EMBODIMENTS

The embodiments of the disclosure include tissue sample cassettes fortransportation and/or other processing of tissue samples for biopsy andpathological procedures. The tissue sample cassettes may includemultiple compartments, such as individualized compartments (e.g., wellsor cavities) sized and configured for retention of collected tissuesamples. The tissue sample cassettes may contain absorbent materialcontaining a volume of liquid, such as formalin and/or an RNApreservative, accessible to the individualized compartments of thetissue sample cassette for fixation and/or preservation of the tissuesamples retained therein. The compartments may also be configured tofacilitate an automated grossing process, wherein an imaging system isutilized to obtain images, measure dimensions of the tissue samplesbased on the obtained images, record collected data, and prepare imagesof the tissue samples in order to expedite the grossing process andsubsequent pathology procedures. As used herein, the term “and/or”includes any and all combinations of one or more of the associatedlisted items.

FIG. 1 shows a top perspective view of a tissue sample cassette 100(also referred to herein as “cassette 100” for simplicity) for biopsyand pathology transportation and/or processing according to anembodiment of the disclosure. FIG. 2 shows an exploded top perspectiveview of the cassette 100 of FIG. 1 and FIG. 3 shows a front view of thecassette 100. In addition, FIG. 4 shows a back view of the cassette 100,FIG. 5 shows a left side view, FIG. 6 shows a right side view, FIG. 7shows a top plan view, and FIG. 8 shows a bottom view of the cassette100.

Referring to FIGS. 1-3, the tissue sample cassette 100 may include agenerally rectangular structure including an upper tray 102, a lowertray 104, and a cover 142 (shown in FIG. 2). In some embodiments, eachof the upper tray 102, the lower tray 104, and the cover 142 may beseparate components, each component of the cassette 100 being sized andconfigured to be releasably secured to one another and collectivelyreferred to as the tissue sample cassette 100. For example, the uppertray 102 may be releasably secured to the lower tray 104 using afriction fit, retention slots, clips, or other such engagement members.Similarly, the cover 142 may be releasably secured to the upper tray 102and/or to the lower tray 104. The upper tray 102 of the cassette 100 mayinclude a top wall 106 extending between a front wall 108 and a backwall 110 opposite the front wall 108. In addition, the top wall 106 mayextend between a first sidewall 112 and a second sidewall 114 oppositethe first sidewall 112.

The lower tray 104 may include a base portion 116 and a recess 140defined by sidewalls 138 extending upward from an upper surface 136 ofthe base portion 116. The recess 140 of the lower tray 104 may be sizedand configured for retaining an absorbent material 134 (e.g., apre-wetted sponge) to facilitate retention and preservation of a tissuesample to be positioned thereon. The absorbent material 134 may containan RNA-preserving solution, for example, a solution comprising anaqueous solvent and an RNA preservative. Alternatively or additionally,another volume of liquid, such as formalin, saline solution, a chemicalfixative, and/or water, may be disposed within the recess 140 to atleast partially saturate the absorbent material 134. The sidewalls 138of the lower tray 104 may define a generally rectangular structure thatmay be sized and configured to be slidably retained within and proximatea complementary generally rectangular structure defined by each of thefront wall 108, the back wall 110, the first sidewall 112, and thesecond sidewall 114 of the upper tray 102. In other words, the twogenerally rectangular structures may be slidably engaged with anotherwhen the cassette 100 is assembled. Further, the upper tray 102 and thelower tray 104 may provide a water-tight or water-resistant seal aroundthe sidewalls thereof when assembled.

The cassette 100 may be formed of any material that is compatible with(e.g., not reactive with) liquids to which the cassette 100 may beexposed, such as formalin, an RNA preservative, saline solution, achemical fixative, or water. By way of example, the cassette 100 may beformed of a polymer material (e.g., thermosetting polymers,thermoplastic polymers, polyethylene, polyvinyl chloride, polypropylene,polystyrene, polycarbonate, acetal, silicone), a metal material (e.g.,aluminum, stainless steel), or a composite material (e.g., fiberglass,carbon fiber composite, aramid fiber composite). Further, at least thecover 142 may be clear (e.g., transparent) for imaging of tissue samplestherethrough, as discussed in further detail below. By way of exampleand not limitation, the cassette 100 may be manufactured by injectionmolding, machining, extruding, thermoforming, 3D printing, or acombination of such processes. The cassette 100 may be one integralpiece or multiple pieces that are secured together. For example,components of the cassette 100 may be constructed to be form fitted(e.g., vacuum formed over a mold) to ensure like sizes and shapes amongcomponents. In some embodiments, the cassette 100 may be manufactured byextrusion followed by machining or stamping, by injection molding, by 3Dprinting, by casting, or by machining, for example.

The base portion 116 of the lower tray 104 may further include a tab 118for ease of grasping the lower tray 104 while opening and closingseparate components of the cassette 100. The tab 118 may be located, forexample, proximate the back wall 110 of the upper tray 102 when thecassette 100 is assembled. Similarly, the cover 142 may include a tab144 that is complementary to the tab 118 of the lower tray 104 for easeof grasping the cover 142 while opening and closing the separatecomponents of the cassette 100. In some embodiments, the tab 118 of thelower tray 104 and the tab 144 of the cover 142 may be directly orpartially aligned with one another. In other embodiments, the tab 118 ofthe lower tray 104 and the tab 144 of the cover 142 may not be alignedwith one another, but may be proximate one another on the same side ofthe cassette 100. In yet other embodiments, the tab 118 of the baseportion 116 and the tab 144 of the cover 142 may be located on oppositeor adjoining sides of the cassette 100. In some embodiments, the uppertray 102 may also include a similar tab to facilitate assembly ordisassembly of the cassette 100.

As shown in FIGS. 1-3, multiple (e.g., six) compartments 120 may beseparated by dividers 126 extending from the front wall 108 to proximatethe back wall 110 of the upper tray 102. By way of example, the tissuesample cassette 100 may include six compartments 120 for retainingrespective tissue samples. In other embodiments, the tissue samplecassette 100 may include fewer or more compartments 120 (e.g., 4-12compartments 120), depending on, for example, the size and shape of thecompartments 120, the size and shape of the cassette 100, and/or theshape, quantity, and size of tissue samples to be collected from apatient in a particular procedure. For example, the quantity ofcompartments 120 may be selected to correspond to compartments ofholders or trays (e.g., a matrix including a block of matrix material)for subsequent tissue processing. For example, a suitable matrix forreceiving tissue samples for histological processing is disclosed inU.S. Patent Publication No. 2014/0135236 to Musat (“the '236Publication”), which is assigned to the Assignee of this disclosure, andthe disclosure of which is incorporated herein in its entirety by thisreference. The '236 Publication discloses a matrix block that may beused in collecting and processing groups of six biopsies, for example.When such a matrix block is to be used for subsequent processing, atissue sample cassette 100 according to this disclosure having sixcompartments 120 may be selected and utilized.

Each of the compartments 120 may have a proximal end portion 121 at orproximate the front wall 108 of the upper tray 102 and a distal endportion 122 proximate the back wall 110 of the upper tray 102. Thecompartments 120 may be sized, shaped, and configured to receive andretain respective tissue samples therein. In the embodiment shown inFIGS. 1-8, the compartments 120 may be arranged laterally between andsubstantially parallel to the first sidewall 112 and the second sidewall114 of the upper tray 102 to retain tissue samples therein in asubstantially horizontal orientation. Further, each of the compartments120 may be elongated and separated by the dividers 126, which may alsobe elongated, to facilitate processing of tissue samples extractedduring needle-core biopsy procedures. Alternatively, in additionalembodiments, the compartments 120 may have a different shape (e.g.,circular, square, rectangular, etc.) to accommodate tissue samples ofdifferent types (e.g., dermatological samples, shaves, punches,excisions, etc.), sizes, and shapes.

As used herein, the term “substantially” in reference to a givenparameter, property, or condition means and includes to a degree thatone skilled in the art would understand that the given parameter,property, or condition is met with a small degree of variance, such aswithin acceptable manufacturing tolerances. For example, a parameterthat is substantially met may be at least about 90% met, at least about95% met, or even at least about 99% met.

However, additional sizes and configurations of the compartments 120 andthe dividers 126 are envisioned. For example, the compartments 120 maybe rectangular, square, circular, or oval in shape and may be configuredto facilitate tissue samples collected during procedures other thanneedle-core biopsy procedures. For example, the compartments 120 may beprovided in different sizes and shapes, and the medical professionaltaking the biopsy may select the tissue sample cassette having theappropriate size and shape to accept a particular type, shape, and sizeof biopsy.

Referring again to FIGS. 1-3 and 7, the dividers 126 of the compartments120 may also be arranged laterally between and substantially parallel tothe first sidewall 112 and the second sidewall 114 of the upper tray102. Inner sidewalls 128 of the dividers 126 may extend downward fromthe top wall 106 of the upper tray 102. In some embodiments, the innersidewalls 128 may be substantially planar and vertical. In otherembodiments, the inner sidewalls 128 of the dividers 126 may benonplanar and/or angled. For example, the inner sidewalls 128 may betapered or at least partially tapered to facilitate retention andretrieval of tissue samples retained in the compartments 120. In someembodiments, the inner sidewalls 128 may include multiple portionshaving differing slopes relative to one another. For example, the innersidewalls 128 may include a lower vertical sidewall 128 a, an inclinedsidewall 128 b, and an upper vertical sidewall 128 c. By way ofnon-limiting example, each of the lower vertical sidewall 128 a and theupper vertical sidewall 128 c may be substantially vertical andtransverse (e.g., perpendicular) with respect to the top wall 106 of theupper tray 102, while the inclined sidewall 128 b may bridge the lowervertical sidewall 128 a and the upper vertical sidewall 128 c and may beoriented at an angle (e.g., between about 30° and 40°) with respect tothe top wall 106 of the upper tray 102. Further, the lower verticalsidewall 128 a may be about 1.5 mm in height above an upper surface ofthe absorbent material 134. Such a “tapered” configuration of the innersidewalls 128 of the dividers 126 may facilitate retention and retrievalof the tissue samples. Further, retention and retrieval of the tissuesamples may also be facilitated by the upper surface of the absorbentmaterial 134 having a concave (e.g., domed) aspect in a lateralcross-section of each of the compartments 120, which concave shape maybe obtained by the dividers 126 pressing down on the upper surface ofthe absorbent material 134 when the cassette 100 is assembled.Optionally, in some embodiments, an upper surface of the absorbentmaterial 134 may include one or more cutouts 135, shown in FIG. 2 indashed lines, to facilitate receipt and retention of tissue samples. Thecutouts 135 may have one or more of various sizes and shapes, which maybe selected to receive various tissue sample shapes and sizes. By way ofexample, the cutouts 135 may have a circular shape with a diameterselected to receive a dermatological punch biopsy of a predeterminedsize.

Each of the compartments 120 and the dividers 126 may extend across onlya portion of the top wall 106 between the front wall 108 and the backwall 110 of the upper tray 102. For example, each of the compartments120 and the dividers 126 may extend from at or proximate the front wall108 while not fully extending to the back wall 110 of the upper tray102. In other words, the compartments 120 and the dividers 126 may notextend to the back wall 110. Rather, an area of the top wall 106 betweenthe distal end 122 of the compartments 120 and the back wall 110 may bereserved for identifiers 124 of the respective compartments 120. Forexample, alphanumeric indicators (e.g., Arabic numerals, letters) may belocated on the top wall 106 between the distal end 122 of each of thecompartments 120 and the back wall 110 of the upper tray 102, as shownin FIGS. 1-7. As shown in FIGS. 4-6, an outer surface of the identifiers124 may be raised relative to an outer surface of the top wall 106 ofthe upper tray 102. However, the identifiers 124 may be placed in anyconfiguration (e.g., location, position, or orientation) in order tofacilitate identification and orientation of respective compartments 120and may include any type of indicator (i.e., symbol) in order touniquely identify each of the compartments 120 to facilitate tracking ofbiopsy source locations. In some embodiments, the identifiers 124 may beprovided in another manner, such as by printing, applying printedadhesive decals (e.g., stickers), or forming recessed identifiers 124,for example. At present, a medical professional typically records aposition of tissue samples either manually (i.e., hand-written labels)or electronically by utilizing computerized software, for example. Insome embodiments, systems may be provided in order to facilitatetracking of extraction location using the identifiers 124. For example,a user may have access to computerized programs having serially listedfields (e.g., 1-6) corresponding to each of the compartments 120 forentering (e.g., typing, selecting an option from a menu or graphic,speaking the location into a microphone for voice-recognitionprocessing) the corresponding extraction information. By way ofnon-limiting example, such computerized programs may include drop-downmenus in user interface displays. The drop-down menus for each of thefields (e.g., 1-6) may include one or more selection options and a tablehaving multiple fields to assist a user with assigning information to besynchronized with a database, which drop-down menus may contain commonlyused biopsy information (e.g., extraction locations) for specifiedprocedures.

In addition, the identifiers 124 and/or other such markers may beconfigured to indicate the orientation of the cassette 100 to ensure thesame orientation thereof during various stages of processing, which maybe beneficial in tissue sample collection procedures (e.g., samplecollection procedures of gall bladder, prostate core biopsy, ortransverse vessel samples) requiring an appropriate specimen orientationto be maintained for pathologic radiologic correlation. In someembodiments, a layout of the cassette 100 may mimic location andorientation of extraction locations, and the compartments 120 may besimilarly oriented such that source extraction locations may matchlocation and orientation (e.g., organ map) of at least some of thecompartments 120 in the cassette 100.

In some embodiments, each of the compartments 120 may be characterizedas “wells” and may optionally include an opening 130 (e.g., recess)defined by two opposing lower vertical sidewalls 128 a and a bottomportion extending therebetween in the front wall 108 of the upper tray102. The opening 130 may be sized and configured to facilitate insertionof a needle in a respective compartment 120 and to enable a user to pullthe needle toward the proximal end 121 thereof while depositing a tissuesample (e.g., prostate) taken during a needle-core biopsy procedure.Further, the opening 130 may ensure orientation maintenance during sucha procedure, given the accessibility of the compartments 120 through theopening 130 of the front wall 108, which provides unidirectional accessof the needle.

In some embodiments, each of the first sidewall 112 and the secondsidewall 114 may not be uniform in height between the front wall 108 andthe back wall 110 of the upper tray 102. For example, each of the firstsidewall 112 and the second sidewall 114 of the upper tray 102 may havea relatively greater height with respect to the base portion 116 of thelower tray 104 proximate the back wall 110 of the upper tray 102 and mayhave a relatively lesser height with respect to the base portion 116 ofthe lower tray 104 proximate the front wall 108 of the top tray 102. Inother words, the top wall 106, including each of the compartments 120and the dividers 126, may slope downward from the back wall 110 to thefront wall 108 of the upper tray 102. Further, the sidewalls 138 of thelower tray 104 may be correspondingly sloped to accommodate the slopedsurface of the upper tray 102. Such a sloped configuration mayfacilitate deposition and alignment of the tissue sample into each ofthe compartments 120. In addition, the sloped configuration may furtherfacilitate automated imaging and processing (e.g., grossing) of thespecimen, as discussed in further detail below. Further, the cover 142may be sized and configured to correspond to the sloped configuration ofthe upper tray 102 and the lower tray 104.

In addition, the inner sidewalls 128 of the dividers 126 may includedepth markers 132 (e.g., scribe lines) to facilitate measurement of thetissue samples. For example, the depth markers 132 may include generallyhorizontal lines, grooves, or marks extending substantially parallel tothe top wall 106 and along the inner sidewalls 128 of the dividers 126of one or more (e.g., each) of the compartments 120. The depth markers132 may be located on one or both of the inner sidewalls 128 and mayextend from proximate to the proximal end 121 to proximate the distalend 122 of the compartments 120. In some embodiments, the depth markers132 may also include generally vertical lines or marks extendingsubstantially perpendicular to the top wall 106 and from proximate thetop wall 106 to proximate a base of the lower vertical sidewalls 128 aof the inner sidewalls 128 of the dividers 126 of one or more (e.g.,each) of the compartments 120. In yet other embodiments, an optical orimaging system may include a reticle grid in a lens thereof in additionto or instead of the depth markers 132. By way of non-limiting example,the depth markers 132 may include a 1 mm grid pattern to aid in sizingthe tissue samples. The depth markers 132 may facilitate manual and/orautomatic measurement of tissue samples. For example, horizontal linesor marks may be used to ascertain a height of a sample, while verticallines or marks may be used to ascertain a length of a sample. Suchmeasurements may be used, in turn, to determine an approximation of anarea covered by the tissue sample.

In some embodiments, the top wall 106 of the upper tray 102, includingthe dividers 126 of the compartments 120, may be configured to bepositioned above an upper surface of the absorbent material 134. In thisconfiguration, the volume of liquid (e.g., formalin, RNA preservative,etc.) may be available to each of the compartments 120 such that anupper surface of the absorbent material 134 is proximate (e.g., inphysical contact) with a lower edge of each of the compartments 120. Byway of example and not limitation, an upper surface of the absorbentmaterial 134 may be in direct physical contact with a lower edge of thelower vertical sidewalls 128 a of the inner sidewalls 128 of thedividers 126. In this manner, the tissue sample cassette 100 may providea single source of preservative fluid for the tissue samples withoutrequiring the tissue samples to be suspended in fluid (e.g., formalin)during collecting, transporting, and/or processing of the tissuesamples. At present, tissue samples are typically transported from aclinic to a laboratory using vessels (e.g., bottles) of formalin. Suchprocesses typically require large amounts of fluid to float each tissuesample in individual bottles. Alternatively, trays (e.g., cassettes) areknown in the art. Such trays are typically transported within bottlesfilled with formalin, or fluid courses or conduits pass between openingsin the surfaces of the trays, which trays are typically filled with afluid (e.g., formalin) at first use. Therefore, use of the cassette 100including the absorbent material 134 (e.g., pre-wetted sponge) enablesconvenience of use while excluding the need to float tissue samples influid, to handle and use large amounts of fluid (e.g., formalin) andwithout requiring multiple individual bottles.

As shown in FIG. 2, the cover 142 may include indentations 146 in a topwall thereof. The indentations 146 may correspond to and be aligned withrespective compartments 120 of the upper tray 102 to facilitate assemblyof the tissue sample cassette 100 and to maintain orientation of thetissue samples within the compartments 120. For example, theindentations 146 of the cover 142 may be elongated and may extend from afront wall thereof to proximate a back wall thereof. For example, thecover 142 may include six individual indentations 146 corresponding tosix respective compartments 120 of the upper tray 102. In addition, theindentations 146 may be separated by elongated portions of the cover 142lacking indentations corresponding to respective dividers 126 of thecompartments 120. In addition, the indentations 146 may includesidewalls configured to correspond to the size and shape of the innersidewalls 128 of the dividers 126 and may be form fitted thereto.Further, the indentations 146 may be recessed to a designated depth tofacilitate a lower portion thereof to be proximate (e.g., touching) anupper surface of the absorbent material 134 and/or an upper surface ofthe tissue samples to facilitate retention and alignment thereof withinthe respective compartments 120 and to inhibit the tissue samples frommoving and/or falling out of the compartments 120 during transportation.In addition, an underside surface of the cover 142 may be treated with ahydrophobic material (e.g., NEVERWET® hydrophobic coating products)commercially available through NeverWet, LLC of Lancaster, Pa., toreduce (e.g., hinder or restrict) the tissue samples from adhering tothe underside surface of the cover 142.

In addition, a water-tight or water-resistant seal may be created in thecassette 100, when assembled, to facilitate fluid retention in theabsorbent material 134 during storage and transportation of the tissuesamples. Further, at least a portion (e.g., an outer surface) of theabsorbent material 134 may include a hydrophilic material to furtherfacilitate fluid retention therein and to deter the absorbent material134 from drawing moisture from the tissue sample during transportationand/or processing thereof. In some embodiments, all or portions of anunused tissue sample cassette 100 may be further sealed (e.g., shrinkwrap, blister pack, etc.) to ensure fluid retention in the absorbentmaterial 134 prior to first use. Further, the cover 142 may be sized andconfigured to accommodate the lower tray 104 of an additional cassette100 to be placed thereon in a stacked arrangement. In other words, thecover 142 may be form fitted to nest within the lower tray 104 of theadditional cassette 100.

As shown in FIG. 8, the lower tray 104 may include a lower surface 148of the base portion 116. A tracking element 150 may be positioned in arecess or adhered to an outer surface of the lower surface 148. Thetracking element 150 may be a machine- and/or human-readable device orlabel including, for example, a barcode label, a written (e.g., printedor hand-written) label, a serial number label, or multiple alternativetypes of tissue sample tracking elements. In some embodiments, thetracking element 150 may be configured to facilitate automatic readingthereof for entry into an automated system, which device or label mayuniquely identify tissue samples and, by virtue of an identificationcode, may identify evaluation, processing, and/or tests to be conductedthereon. In some embodiments, the tracking element 150 may include aradio-frequency identification (RFID) tag. In other embodiments, thetracking element 150 may include a near field communication (NFC) deviceor other such machine-readable or electronically transferable trackingdevice. Optionally, the cassette 100 may include a space (e.g., on theupper tray 102, on the lower tray 104, and/or on the cover 142) forpositioning labels to identify, for example, each of the compartments120. For example, a space may be provided adjacent to the identifiers124 to affix or otherwise provide a label for each of the compartments120. Such labels, if present, may identify information relating to thetissue sample in each of the respective compartments 120, such asorientation of the tissue sample, location on an organ from which thetissue sample was taken, etc.

The tracking element 150 may be positioned on the lower surface 148 asshown in the embodiment of FIG. 8 to facilitate tracking andidentification of the cassette 100. The tracking element 150 may reducethe likelihood of misidentification of tissue samples within each of thecassettes 100, and may further provide additional informationcorresponding to the tissue samples (e.g., doctor notes, patient name,patient age, patient gender, type of tissue sample(s), processinginstructions). Such additional information may be stored in a networkeddatabase and identified with an identification or serial numberassociated with the tracking element 150. Further, the tracking element150 may be positioned to be read (e.g., scanned) by a reader associatedwith an imaging device, as discussed in further detail below. In otherembodiments, a reader may or may not be associated with an imagingdevice, and the tracking element 150 may be used for orientationconfirmation of the cassette 100. In addition, the tracking element 150may be located on an exterior surface of any one of the upper tray 102,the lower tray 104, or the cover 142. The location of the trackingelement 150 on the cassette 100 may, however, be determined by therelative position of the reader to the cassette 100 during processing.For example, the lower surface 148 of the lower tray 104 may bepositioned above the reader while an upper surface of the cassette 100(e.g., cover 142 or upper tray 102) may be positioned below an imagingdevice (e.g., camera) positioned and configured to capture images of thetissue sample through the upper surface of the cassette 100 duringprocessing, as discussed in further detail below.

FIG. 9 is a simplified block diagram of an imaging system 200 forautomatically registering the tissue sample cassette 100 shown in FIGS.1-8. The imaging system 200 may include an imaging device 202 (e.g.,camera) to obtain images (e.g., monochrome or color) of tissue sampleswithin the cassette 100. A tracking element reader 204 may be associatedwith the imaging system 200. The tracking element reader 204 may bepositioned and configured to read (e.g., scan) the tracking element 150.The imaging system 200 may further include a processor 206 includingmemory 208 as well as a data storage unit 210 (e.g., external). Theprocessor 206 may be in communication with each of the imaging device202 and the tracking element reader 204.

As described in greater detail above, the tracking element reader 204may be positioned to be below the lower surface 148 of the lower tray104 to facilitate reading (e.g., scanning) of the tracking element 150when the cassette 100 is presented for processing. The processor 206 maybe configured to accept unique identification information from thetracking element 150 to enable processing (e.g., inputting, storing,classifying, etc.) information associated with records stored in thedata storage unit 210.

The imaging device 202 may be positioned to be located above thecassette 100 for capturing one or more images (e.g., digital images) ofthe tissue samples when the cassette 100 is presented for processing.The imaging device 202 may be positioned and configured to obtain imagesfrom above, for example, with an optical axis of the imaging device 202being transverse (e.g., perpendicular) to a surface (e.g., platform,table top, etc.) upon which the cassette 100 rests. In some embodiments,an optical axis of the imaging device 202 may not be located directlyabove, but may be positioned at a non-vertical angle with respect to thesurface upon which the cassette 100 rests. For example, the imagingdevice 202 may be positioned to utilize the forward-sloping aspect ofthe cassette 100. The imaging device 202 may be equipped with anappropriate lens (e.g., camera lens) having a field-of-view adequate toview each of the compartments 120 of the cassette 100 in sufficientdetail, including tissue samples placed therein. Further, the imagingdevice 202 may be configured for obtaining specific dimensions (e.g.,height, length, area, etc.) of tissue samples. In some embodiments, theimaging device 202 may include one or more specialized cameras (e.g., 3Dcamera), multiple cameras at various angles, and/or various lightingconditions to assist in obtaining the measurements of the tissuesamples. Such measurements may be obtained with the aid of the depthmarkers 132, as described above.

In addition, holding trays may be utilized within the imaging system 200to facilitate processing of the tissue samples within the cassette 100.For example, the holding trays may provide a structure to aid inpositioning the cassette 100 during processing (e.g., scanning, imaging,etc.) to facilitate the automated processing thereof. In other words,the holding trays may be utilized to promote proper alignment of thecassette 100 with the tracking element reader 204 and/or the imagingdevice 202. In addition, the holding trays may be sized and configuredto accommodate known trays and cassettes of any source and/orconfiguration to facilitate processing by the imaging system 200. Inthis manner, in some embodiments, tissue samples may be automaticallyregistered as part of the grossing processing without requiring the useof the particular cassette 100 disclosed above.

Images of tissue samples obtained by the imaging device 202 may then bereceived and stored in the memory 208 of the processor 206. The memory208 may include or be associated with an algorithm (e.g., artificialintelligence, deep learning) configured to recognize (e.g., identify)tissue samples based on the captured images. The algorithm may betrained to accurately recognize the tissue samples and to calculategross measurements thereof. One or more deep-learning algorithms may betrained using particular attributes of selected tissue samples stored inthe memory 208 and/or the data storage unit 210. For example, suchdeep-learning algorithms may be trained using at least a portion of theattributes of current and/or previous tissue samples or using providedinformation, such as from an external database, for example. The traineddeep-learning algorithms may be used by the processor 206 to rendermeasurements of the tissue samples. For example, the algorithms mayprocess the captured images using the processor 206 to discern thetissue samples from a background (e.g., materials of the cassette 100)for accurate locating and dimensioning of the tissue samples. In otherembodiments, the algorithms may be utilized to recognize certain aspectsof specific tissue samples. Information obtained from determining themeasurements (e.g., height, length, area) of the tissue samples may thenbe used as part of the required gross description thereof. In thismanner, the imaging system 200, including the processor 206, may providegross measurements as well as one or more images of the tissue samplecaptured by the imaging device 202.

In some embodiments, the cassette 100 of this disclosure may facilitateand improve the process of obtaining gross measurements described hereinby maintaining the tissue samples in substantially consistent and knownorientations relative to the features of the cassette 100. Thealgorithms may be configured to identify the features of the cassette100 from the images obtained by the imaging device 202 and todistinguish the tissue samples from and compare portions of the tissuesamples to those features. Accordingly, the cassette 100 may enableimproved and more efficient tissue sample detection and grossmeasurements thereof, potentially including depth measurements andmeasurements of multiple tissue samples in a single cassette 100.

The gross measurements and/or images may then be associated with records(e.g., patient records) stored in the memory 208 and/or the data storageunit 210. The algorithm stored within the memory 208 of the processor206 may then provide a written description, which may or may not includediscrete values of the measurements, and/or a visual representation ofthe measurements as a portion of the grossing process. The automatedgrossing process includes steps to identify regions (e.g., theidentifiers 124, the depth markers 132, etc.) of the cassette 100, torecognize the tissue samples, and to associate the gross measurementsthereof with one or more of the identified regions of the cassette 100.Such a process enables linking the collected tissue samples, utilizingthe identified regions of the cassette 100, with one or more distinctcollections of tissue samples (e.g., known tissue samples). In someembodiments, utilizing multiple images with varying lighting conditionsmay increase accuracy of the deep-learning algorithm. Further,additional pre-processing and post-processing steps may allow the imagesto be normalized and smoothed to produce results consistent with theneeds of the user.

In use, the tissue sample cassette 100 may be utilized in atissue-collection procedure (e.g., needle-core biopsy) performed at aclinic or other medical facility. To prepare the cassette 100 for use,each of the tab 144 of the cover 142 and the tab 118 of the lower tray104 may be grasped and pulled in opposite directions to remove (e.g.detach) the cover 142 from each of the upper tray 102 and the lower tray104, which may remain assembled to one another, retaining the absorbentmaterial 134 therebetween. The identifiers 124 of the compartments 120may indicate a proper orientation in which to place the cassette 100during the procedure. Further, the identifiers 124 may be used to tracklocations and orientations of harvested tissue samples, as described ingreater detail above.

One or more tissue samples may be collected from a patient during theprocedure and the collected tissue samples may then be placed withinrespective compartments 120 of the cassette 100. For example, tissuesamples (e.g., prostate samples) taken from a patient during a biopsyprocedure may be deposited within the respective compartments 120. Asthe tissue samples are deposited into the respective compartments 120,information associated therewith may be logged into an anatomicpathology system (e.g., manually or automatically) to facilitateinputting and tracking of such information. For example, computerizedprograms including fields (e.g., utilizing drop-down menus, graphics,etc.) for entering the corresponding extraction information may beutilized. In addition, the tracking element 150 may facilitate linkingthe extraction information of collected tissue samples contained withinthe cassette 100 with respective patients, organs, and/or procedures.

Following the biopsy procedure, the cassette 100 may be reassembled byreplacing the cover 142 and ensuring a tight seal by utilizing each ofthe tab 144 of the cover 142 and the tab 118 of the lower tray 104, forexample. During transportation and subsequent processing, the absorbentmaterial 134 (e.g., pre-wetted sponge) may maintain moisture within thecassette 100 for an extended period of time prior to first use andduring transportation and/or processing of the collected tissue samples.The tissue sample cassette 100 may then be transported to a pathologylaboratory for further processing (e.g., grossing) of the collectedtissue samples using the imaging system 200, including the imagingdevice 202 and/or the tracking element reader 204. In some instances,the cassettes may not be transported to a laboratory for the grossingprocedure. Rather, the grossing procedure may be performed at the clinicor medical facility (e.g., the point-of-care) using an on-site imagingsystem 200. The cassette 100 may then be transported to a pathologylaboratory for further processing (e.g., diagnostic studies) once thegrossing process has been completed at the location where the biopsy wastaken. In some embodiments, information obtained by the imaging system200 may be presented to a pathologist for review. The pathologist mayreview the image(s) obtained by the imaging system 200, and may provideadditional gross measurements or testing to manually complete thegrossing process. In addition, the pathologist may be able to provide animproved analysis (e.g., diagnosis) of the tissue sample by reviewingthe image(s) of the tissue sample as the tissue sample was taken at theclinic or medical facility. Tissue sample attributes may change duringtransportation from the clinic or medical facility to a laboratory.Accordingly, providing the image(s) of the tissue sample taken at theclinic or medical facility in a standardized platform (e.g., in thecassette 100) may facilitate pathological procedures and improve patientcare.

One or more cassettes 100 may be presented to initiate the automatedgrossing process using the imaging system 200. The tracking element 150may be read (e.g., scanned) with the tracking element reader 204. Insome embodiments, the cassette 100 may be positioned and/or passed(e.g., swiped) over the tracking element reader 204 positioned below thelower tray 104 of the cassette 100. In addition, the tissue samples maybe presented for imaging using the imaging device 202 by aligning thecassette 100 with the imaging device 202 positioned proximate (e.g.,above) the cassette 100. In some embodiments, the cover 142 may beremoved prior to obtaining images. In other embodiments, the cover 142may be clear (e.g., transparent) to facilitate imaging therethrough. Thesloped aspect of the cassette 100 may facilitate the imaging process. Insome embodiments, reading the tracking element 150 with the trackingelement reader 204 and imaging the cassette 100 with the imaging device202 may be done substantially at the same time (e.g., simultaneously).In other embodiments, the reading of the tracking element 150 and theimaging of the cassette 100 may not be done at the same time, but may bedone before or after one another. Further, positioning the cassette 100within the imaging system 200 may be done manually by a user and/or byusing an automated process for handling the cassette 100 and/orinitiating the grossing process. In some embodiments, the cassette 100and/or known trays or cassettes may be placed in holding trays prior toprocessing with the imaging system 200. In such configurations, thetracking element 150 may or may not be associated with the holding traysrather than the individual cassette 100.

Once the cassette 100 is positioned proximate the imaging device 202,the imaging device 202 (e.g., camera) may capture images of the tissuesamples disposed within the compartments 120 of the cassette 100. One ormore images (e.g., digital images) may be obtained during the grossingprocess, as described in greater detail above. If needed, the cover 142may then be reassembled with the lower tray 104 and the cassette 100 maybe stacked or otherwise packaged for transportation and/or furtherprocessing. The captured images of the tissue samples may be linked withelectronic records (e.g., patient records) associated with the trackingelement 150. The processor 206 using the deep-learning algorithm maythen be utilized to recognize the tissue samples and to calculate grossmeasurements, as described in greater detail above. Once the grossingprocess has been completed, the gross measurements and images of thetissue samples may be associated with individual electronic records andutilized during subsequent processing, diagnosing, and/or reporting.

The following description provides specific details, such as materialtypes, manufacturing processes, uses, and structures in order to providea thorough description of embodiments of the disclosure. However, aperson of ordinary skill in the art will understand that the embodimentsof the disclosure may be practiced without employing these specificdetails. Indeed, the embodiments of the disclosure may be practiced inconjunction with conventional manufacturing techniques and materialsemployed in the industry.

In the preceding detailed description, reference is made to theaccompanying drawings, which form a part hereof, and in which is shown,by way of illustration, specific embodiments in which the disclosure maybe practiced. These embodiments are described in sufficient detail toenable a person of ordinary skill in the art to practice the disclosure.However, other embodiments may be utilized, and structural, procedural,and other changes may be made without departing from the scope of thedisclosure. The illustrations presented herein are not meant to beactual views of any particular system, device, structure, or process,but are idealized representations that are employed to describe theembodiments of the disclosure. The drawings presented herein are notnecessarily drawn to scale. Similar structures or components in thevarious drawings may retain the same or similar numbering for theconvenience of the reader; however, the similarity in numbering does notmean that the structures or components are necessarily identical insize, composition, configuration, or other property.

As used herein, any relational term, such as “first,” “second,” “top,”“bottom,” “upper,” “lower,” “front,” “back,” “above,” “below,”“horizontal,” “vertical,” etc., is used for clarity, consistency ofterminology, and convenience in understanding the disclosure andaccompanying drawings and does not connote or depend on any specificpreference, orientation, or order, except where the context clearlyindicates otherwise. For example, the disclosure includes tissue samplecassettes that may be rotated or flipped in use such that the topthereof faces down and the bottom thereof faces up, and/or the frontfaces away from the user and the back faces toward the user. Thus, whileone example orientation of tissue sample cassettes is used herein forclarity, other possible orientations are contemplated by, and areincluded in, the disclosure.

The embodiments of the disclosure described above and illustrated in theaccompanying drawing figures do not limit the scope of the invention,since these embodiments are merely examples of embodiments of thedisclosure. The invention is encompassed by the appended claims andtheir legal equivalents. Any equivalent embodiments lie within the scopeof this disclosure. Indeed, various modifications of the disclosure, inaddition to those shown and described herein, such as other combinationsand modifications of the elements described, will become apparent tothose of ordinary skill in the art from the description. Suchembodiments, combinations, and modifications also fall within the scopeof the appended claims and their legal equivalents.

1. A system for automated gross processing of tissue samples in a tissuesample cassette, comprising: tissue sample cassette comprising atracking element; a cover for holding the tissue sample cassette, thecover being substantially transparent such that at least one imagingdevice can obtain images of tissue samples positioned within the tissuesample cassette through the cover; a tracking element reader configuredto read information from the tracking element of the tissue samplecassette; and a processor associated with the tracking element reader,the processor in communication with memory configured to store theimages of the tissue samples, wherein the processor is programmed torecognize the tissue samples and to determine and provide grossmeasurements for the tissue samples based on the images of the tissuesamples obtained through the cover.
 2. The system of claim 1, whereinthe processor is configured to accept information associated with thetracking element of the tissue sample cassette, the tracking elementbeing read by the tracking element reader.
 3. The system of claim 1,wherein the processor is configured to process information associatedwith records stored in a data storage unit.
 4. The system of claim 1,wherein the gross measurements provided by the processor include atleast one of height, length, or area of the tissue samples.
 5. A methodof providing gross measurements of tissue samples in a tissue samplecassette, the method comprising: supporting a tissue sample cassette ina substantially transparent cover; supporting tissue samples with thetissue sample cassette; acquiring at least one image of the tissuesamples in the tissue sample cassette through the substantiallytransparent cover utilizing an imaging device; and determining grossmeasurements of the tissue samples using a processor programmed torecognize the tissue samples from the at least one image and to providethe gross measurements based on the at least one image.
 6. The method ofclaim 5, further comprising: linking the acquired at least one image andthe gross measurements with records using a tracking element readerconfigured to recognize a tracking element associated with the tissuesample cassette.
 7. The method of claim 5, further comprising:transporting the tissue samples with the tissue sample cassette to apathology laboratory without the tissue samples being suspended in afluid.
 8. The method of claim 5, wherein acquiring at least one image ofthe tissue samples utilizing the imaging device comprises acquiring aplurality of images of the tissue samples with at least one camera. 9.The method of claim 5, wherein determining gross measurements of thetissue samples utilizing a processor comprises using the processor torecognize tissue samples based on the acquired images and based at leastin part on information stored in a data storage unit.